TY - JOUR
T1 - Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols
AU - Yi, Jinsoo
AU - Knudsen, Tine A.
AU - Nielsen, Anne Louise
AU - Duelund, Lars
AU - Christensen, Morten
AU - Hervella, Pablo
AU - Needham, David
AU - Mouritsen, Ole G.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - We have quantified the inhibition of intestinal cholesterol transport by pine-derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1 mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (± 0.17) × 10−6 cm/s. When 0.1 mM β-sitosterol was solubilized alongside, Papp was effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVita™ FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp = 0.06 (± 0.06) × 10−6 cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Papp in the range of 0–0.09 × 10−6 cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system.
AB - We have quantified the inhibition of intestinal cholesterol transport by pine-derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1 mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (± 0.17) × 10−6 cm/s. When 0.1 mM β-sitosterol was solubilized alongside, Papp was effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVita™ FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp = 0.06 (± 0.06) × 10−6 cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Papp in the range of 0–0.09 × 10−6 cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system.
KW - Apparent permeability coefficient
KW - Cholesterol
KW - HT29-MTX intestinal cell model
KW - Pine-derived phytosterols
KW - PinVita™ FSP DuPont
KW - Sterol transport
KW - β-Sitosterol
UR - http://www.scopus.com/inward/record.url?scp=84978839885&partnerID=8YFLogxK
U2 - 10.1016/j.chemphyslip.2016.06.008
DO - 10.1016/j.chemphyslip.2016.06.008
M3 - Journal article
C2 - 27372052
AN - SCOPUS:84978839885
SN - 0009-3084
VL - 200
SP - 62
EP - 73
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
ER -